Southern California Conferences for Undergraduate Research

Southern California Conferences for Undergraduate Research

Reduced chloride conductance causes muscle hyperexcitability and contributes to the motor dysfunctions in Huntington’s disease.


Grigor Varuzhanyan, Christopher Waters


Andrew Voss, Assistant Professor of Biology, California State Polytechnic University Pomona

Huntington’s disease (HD) is a progressive degenerative disorder that leads to cognitive decline, behavioral changes, muscle dysfunction, and eventually death. It has generally been thought that neurodegeneration is the primary cause of the debilitating involuntary contractions that result in chorea and dystonia in HD patients. In this electrophysiological study, we discovered defects in skeletal muscle fibers from the R6/2 transgenic mouse model of HD that can explain, in large part, the involuntary contractions of HD. We found decreases in the chloride conductance (GCl) and membrane capacitance (Cm) in fibers from the R6/2 mice compared to wild type litter mates (WT). Specific GCl was reduced from 11.9 ± 0.8 mS/cm2 in WT (n=14) to 4.04 ± 1.2 mS/cm2 in HD mice (n=9), a 66% reduction. Specific Cm was reduced from 5.12 ± 0.2 μF/cm2 in WT (n=26) to 3.36 ± 0.17 μF/cm2 in HD mice (n=20), a 34% reduction. The density of GCl was reduced from 2.42 ± 0.2 mS/μF in WT (n=14) to 1.04 ± 0.11 mS/μF in R6/2 mice (n=9), a 57% reduction. Decreases in the density of GCl indicate a significant loss of CLC-1, the chloride channel that mediates most of the GCl. Decreases in Cm indicate a loss of plasma membrane from the transverse tubular system, which is responsible for proper muscle contraction. It is well established that mutations in CLC-1 cause the muscle to be hyperexcitable or hyper-responsive and are known to occur in patients with myotonia. The decreases in GCl and Cm that we measured indicate a primary skeletal myopathy that significantly contributes to the symptoms of HD. These defects may help explain the clinical presentation of HD and provide novel targets to diagnose and treat the disease.

Presented by:

Grigor Varuzhanyan


Saturday, November 17, 2012


2:45 PM — 3:00 PM


Bell Tower 1491

Presentation Type:

Oral Presentation